Abstract
New N-(substituted phenyl)-2-(7-hydroxy-4-methyl-2H-chromen-2-ylidene)hydrazine-1-carboxamides (5a-l) was synthesized in two steps using environmentally friendly ultrasound irradiation. The first step involved solvent free synthesis of 7-hydroxy-4-methyl-2H-chromen-2-one (3) by using catalytic amount (10% mol) of FeCl3. The second step involved condensation of intermediate 3 and hydrazine carboxamide HCl analogues (4a-l) under ultrasonic influence in the water-ethanol (2:1) solvent system to obtain the title compounds (5a-l) in good yield. The structure of prepared compounds (5a-l) was confirmed by spectroscopic study. The synthetic strategy described here has many advantages, including a simple procedure and high conversion with quick reaction times. The cytotoxicity was tested on 60 NCI cancer cell lines at 10 mu M and N-(4-chlorophenyl)-2-(7-hydroxy-4-methyl-2H-chromen-2-ylidene)hydrazine-1-carboxamide (5b) showed promising activity with maximum sensitivity against CCRF-CEM, UO-31, RPMI-8226, NCI-H522, and HL-60(TB) with growth percent (GP) of 17.50, 79.67, 80.59, 82.35, and 83.70 respectively. In a DPPH free radical scavenging assay, the compounds 5b and 5d showed promising antioxidant activity with IC50 values of 16.32 +/- 1.29 and 14.28 +/- 1.82 M, respectively. The binding affinity of the target ligands (5a-l) against the active site of FGFR was also investigated using molecular docking. Within the active site of FGFR4, the ligand 5b interacted with four H-bonds with Asp630 (carbonyl function), Glu520 (with amide NH and ArNH), and Ile609 (phenol function), while an imine "N" showed two salt bridges with Asp630 and Glu520. (C) 2021 Elsevier B.V. All rights reserved.